Method for the preparation of unsaturated ketones

ABSTRACT

β-hydroxyketones are prepared by reacting an aldehyde with acetone in the presence of perhydroisoindole or pyrrolidine and water. The resulting β-hydroxyketone is further reacted in the presence of a solvent mixture to produce α-β-unsaturated ketones.

FIELD OF INVENTION

This invention relates to methods for the preparation of α,β-unsaturated ketones represented by general formula (II) (hereinafterreferred to as Compound II) ##STR1## where R is an aliphatic grouphaving a side chain at the 1 position, an alicyclic group which may havesubstituents, a heterocyclic group which may have substituents or aphenyl group which may have substituents, which are important asintermediates for pharmaceuticals and agricultural chemicals, and tomethods for the preparation of β-hydroxyketones represented by generalformula (I) (hereinafter referred to as Compound I) ##STR2## (where R isas defined above), which are synthetic intermediates for the saidcompound.

DESCRIPTION OF RELATED ART

Conventionally known methods for the preparation of Compound II includea method by aldol condensation of aldehyde with acetone [described insuch documents as Ber. 40 4764 (1907)], a method by condensing aldehydewith acetone using piperidine-acetic acid as a catalyst [described insuch documents as Indian J. Chem. 16B 970-972 (1978)], or a method byreacting aldehyde with metal salt of acetoacetic acid (Japanese openpatent No. Sho 57-4930). However, when aldehyde with no α-hydrogen orwith one α-hydrogen is used as a material, the said methods areinappropriate as industrial manufacturing methods because of low yielddue to a large amount of byproducts produced usually or slow reaction,etc.

Existing methods by dehydrating β-hydroxyketones cannot be employedindustrially because of various problems if they are applied toβ-hydroxyketone with one γ-hydrogen in particular.

For instance, a large amount of such an expensive compound as oxalicacid is required in the reaction, in water, using a dicarboxylic acidcatalyst such as oxalic acid (described in such documents as West Germanpatent No. 840,090). It has a problem from the economical viewpoint.

In the reaction using a strong acid catalyst such as sulfuric acid, inwater and acetone (described in such documents as West German openpatent No. 2,426,039), a large amount of β-hydroxyketones remain and ofby products, particularly β, γ-unsaturated ketones, are produced in alarge quantity.

In the reaction using p-toluenesulfonic acid catalyst in an organicsolvent such as benzene [described in such documents as J. Am. Chem.Soc. 81 628-632 (1959)], the reaction proceeds smoothly byazeotropicdehydration. However, isomerization from α, β-unsaturatedketones to β, γ-unsaturated ketones suddenly increase at around the endpoint of the reaction. Therefore it is difficult to control the β,γ-unsaturated ketones.

Known methods for the preparation of β-hydroxyketones include methods bysynthesizing by aldol condensation of aldehyde with acetone [Ber. 404764 (1907), Ann. Chim. (Paris) 6 406-86 (1951)], and methods byreacting aldehyde with alkaline metal salt of acetoacetic acid (Japaneseopen patent No. Sho 55-141429). Generally the yield is low. The latter,in particular, has low yield when aldehyde with one α-hydrogen is used.

The object of this invention is to provide preparation methods forβ-hydroxyketones which can be used in particular for aldehyde with oneα-hydrogen, which is a drawback of the above methods, and preparationmethods for obtaining α, β-unsaturated ketones from the saidβ-hydroxyketones with high yield.

SUMMARY OF THE INVENTION

The inventors carried out various studies to accomplish the aboveobject, and found that it is possible to easily produce correspondingβ-hydroxyketones even if aldehyde with one α-hydrogen is used with highyield by a gentle reaction in an aqueous solution in the presence ofperhydroisoindole and/or pyrrolidine which may have substituents andthat the said β-hydroxyketones are reacted in the presence of acidcatalyst in a 2-phase system of water and water-insoluble organicsolvent so as to give the intended α, β-unsaturated keytones. Thus thisinvention has been completed, that is, this invention is

(1) A method for the preparation of α, β-unsaturated ketones representedby general formula (II) ##STR3## (where R is as defined above) whichcomprises reacting β-hydroxyketones represented by general formula (I)##STR4## (where R is as defined above) in the presence of acid catalystin a mixture solvent of water and water-insoluble organic solvent.

(2) A method for the preparation of α, β-unsaturated ketones representedby general formula (II) ##STR5## (where R is as defined above) whichcomprises that aldehydes represented by general formula (III)

    RCHO                                                       (III)

and acetone are reacted in the presence of one or two or more compoundsselected from the group consisting of perhydroisoindole and pyrrolidinewhich may have substituents as catalysts, in a water solvent, at -40° C.to 60° C., then acetone is distilled to remove, and a water-insolubleorganic solvent is added to the remaining reaction solution to react inthe presence of acid catalyst.

(3) A method for the preparation of β-hydroxyketones represented bygeneral formula (I) ##STR6## (where R is as defined above) whichcomprises that aldehydes represented by general formula (III)

    RCHO                                                       (III)

and acetone are reacted in the presence of one or two or more compoundsselected from the group consisting of perhydroisoindole and pyrrolidinewhich may have substituents as catalysts, in a water solvent, at -40° C.to 60° C.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The preparation methods of this invention are illustrated by reactionequations as follows. ##STR7##

Aldehydes represented by general formula (III) (hereinafter referred toas Compound III)

    RCHO                                                       (III)

(where R is as defined above), used in Process a include aldehydes withside chain at the α position such as isobutanal, 2-methylbutanal,2,2-dimethylpropanal, 2-methylpentanal, 2,2-dimethylbutanal,2,3-dimethylbutanal, 2-methylhexanal, 2-ethylpentanal,2,2-dimethylpentanal, 2,3-dimethylpentanal, 2,4-dimethylpentanal,2-ethyl-3-methylbutanal, 2-ethyl-2-methylbutanal, 2-methylpeptanal and2-methyloctanal; alphatic aldehydes such as cyclohexane carbaldehyde,2-methylcyclohexane carbaldehyde, 3-methylhexane carbaldehyde and4-methylhexane carbaldehyde; heterocyclic aldehydes such as3-formyltetrahydropyran, 4-formyltetrahydropyran,3-formyltetrahydrothiopyran, 3-formyltetrahydrofuran, 2-formyldioxaneand 3-formylpiperidine; benzaldehydes such as benzaldehyde,p-methylbenzaldehyde, p-methylthiobenzaldehyde, p-chlorobenzaldehyde andp-nitrobenzaldehyde; or benzaldehydes with substituents. Compounds usedas catalysts are pyrrolidine represented by the following formula, whichmay be substituted, (hereinafter referred to as the pyrrolidines)##STR8## where, R₁, R₂, R₃ and R₄ are hydrogen or lower alphatic groupsin addition to perhydroisoindole.

Concrete examples of the pyrrolidines include pyrrolidine, andpyrrolidines substituted at the 3 and/or 4 positions such as3-methylpyrrolidine, 3-ethylpyrrolidine, 3,3-dimethylpyrrolidine,3,3-diethylpyrrolidine, 3,4-dimethylpyrrolidine and3,4-diethylpyrrolidine.

Two or more of these catalysts may be used by mixing. The reactioncarried out by mixing, to a mole of Compound III, 1.5 to 20 times moles,preferably 3 to 10 times moles, of acetone; 50 to 2000 ml, preferably200 to 500 ml, of water; and 0.002 to 0.01 moles, preferably 0.01 to0.05 moles, of catalysts of pyrrolidines.

As for a mixing method, Compound III and acetone are mixed in an aqueoussolvent, to which catalysts are added. However the method that acetoneand catalysts are mixed in an aqueous solution, to which Compound III isdropped is preferable from the viewpoint of reduction in byproduct ratioof impurities represented by general formula ##STR9##

A dropping time is preferably 1 to 5 hours, and followed by curing for 1to 7 hours. A reaction temperature differs depending on a materialaldehyde used, because of equilibrium reaction. The temperature is 0° to60° C., preferably 20° to 40° C., for aldehydes with side chain at the αposition, aliphatic aldehydes or heterocyclic aldehydes. Forbenzaldehyde and substituted benzaldehydes, the temperature is -40° to30° C., preferably -20° to 10° C. When a substituted benzaldehyde isused, the more the substituents are electron donative, the more theequilibrium shifts to the material system, and thus the reaction shouldbe carried out at a lower temperature.

After the reaction is completed, the solution is neutralized with suchas hydrochloric acid to make pH 1 to 6, acetone is distilled up todistillation temperature 100° C., and the obtained is used as it is forthe next Process b, or, if Compound I is collected, it is extracted withwater-insoluble organic solvent such as chloroform or benzene, and theextract is concentrated and distilled under vacuum, to give the intendedproduct.

To carry out the reaction of Process b, when the aqueous solutionobtained in the said Process a is used, sulfuric acid, if used as anacid catalyst, is added to the said aqueous solution so as to be anaqueous solution of 10 to 60% by weight of sulfuric acid, andhydrochloric acid, if used, is added so as to be an aqueous solution of3 to 20% by weight of hydrochloric acid.

After it, 200 to 2000 ml, preferably 300 to 600 ml, of organic solventis added to reflux for 0.5 to 10 hours.

When isolated Compound I is used, 200 to 2000 ml, preferably 300 to 600ml, of organic solvent is added to 1 mole of Compound I. 50 to 1000 g,preferably 200 to 400 g, of aqueous solution of 10 to 60% by weight ofsulfuric acid is added if sulfuric acid is used as an acid catalyst, or50 to 1000 g, preferably 200 to 400 g, of aqueous solution of 3 to 20%by weight of hydrochloric acid, if hydrochloric acid is used, and theresulting solution is refluxed for 0.5 to 10 hours.

The concentration of acid catalyst is affected by type of solvent used.Generally, the concentration is made high if a refluxing temperature islow.

After the reaction is completed, the solution is separated and, 100 to500 g of water is added to the organic solvent layer to neutralize to pH2 to 9 with alkaline aqueous solution such as aqueous NaOH solution,then the resulting solution is separated into a water layer and anorganic solvent layer.

The obtained organic solvent layer is concentrated and distilled undervacuum to give the intended Compound II.

In addition to sulfuric acid and hydrochloric acid, such acids asphosphoric acid and oxalic acid can be used for dehydration as an acidcatalyst, but phosphoric acid and oxalic acid are weak acids so that alarge amount is required, being inappropriate from the economicalviewpoint.

A mixture solvent of water and water-insoluble organic acid which canform an aqueous layer and an organic solvent layer is used as acatalyst. Halogenated hydrocarbon solvents such as chloroform anddichloroethane, and aromatic hydrocarbon solvents such as benzene,toluene and xylene are used as the said water-insoluble organic solvent.

EXAMPLES

This invention is further described in detail by reference to thefollowing examples. The range of this invention is not limited at all bythe following examples.

EXAMPLE 1

Into a reaction vessel of 1 l in inside volume were placed 290.5 g (5moles) of acetone, 300 ml of water and 2.2 g (0.03 moles) ofpyrrolidine, to which 72.1 g (1 mole) of isobutylaldehyde was droppedover an hour while being kept at 30° C., and then stirred at 30° C. for2 hours.

After the reaction is completed, the solution was made pH 4 with 35%hydrochloric acid, and heated to distill acetone up to distillationtemperature 100° C. 325.4 g of aqueous acetone solution was obtained asdistillate. An analysis of the aqueous acetone solution by gaschromatography showed 221.6 g of acetone (recovery: 76.3%. Recovery was95.4% if a mole of acetone was regarded to be used for the reaction) and103.8 g of water.

After it, the remaining solution after the aqueous acetone solution wasdistilled was cooled and extracted with 200 ml of chloroform twice. Thechloroform layers were concentrated. The obtained oily product wasdistilled under reduced pressure to give 113.3 g of colorless oilyproduct with boiling point of 80° to 83° C. at 12 mmHg and n_(D) ¹⁶.51.4379 (crude yield: 87.0%)

The product was analyzed by gas chromatography to find that the intendedproduct, 4-hydroxy-5-methylhexane-2-one was 95.1% in purity (yield:82.7% to isobutylaldehyde used).

To the distilled aqueous acetone solution were added 68.9 g of acetoneand 196.2 g of water, then 2.2 g of pyrrolidine. The same operation asthe above was repeated to give the same result.

EXAMPLES 2 to 13

Example 1 was repeated except that the reaction was carried out using adifferent aldehyde and catalysts under conditions shown in Table 1. Theresults are shown in Table 1, including that of Example 1.

                                      TABLE 1                                     __________________________________________________________________________     CompoundNo.                                                                         ##STR10##       aldehyde)amine/(mole ratioAmine as                                                      Time (hr)(°C.)Temperaturebeing                                        droppedWhile aldehyde                                                                   Time (hr)(°C.)Temperature                                             ompletion                                                                             (%)aldehydematerialsused                                                     rawYield                                                                            PropertiesPhysical      __________________________________________________________________________     1                                                                                   ##STR11##      pyrrolidine 0.03                                                                         30  1    30  2 82.7 bp.                                                                           81˜83°                                                           C. (12 mm Hg)                                                                 n.sub.D.sup.14.5                                                              1.4379                    2                                                                                   ##STR12##      3-melthylpyrrolidine 0.05                                                                50  2    50   6                                                                              82.3 bp.                                                                           87˜89°                                                           C. (1 mm Hg)                                                                  n.sub.D.sup.26                                                                1.4478                    3                                                                                   ##STR13##      3,3- dimethylpyrrolidine 0.03                                                            30  1    30  3 94.7 bp.                                                                           83˜86°                                                           C. (0.6 mm Hg)                                                                n.sub.D.sup.17.5                                                              1.4762                    4                                                                                   ##STR14##      pyrrolidine 0.025                                                                        30  1    30  4 85.3 bp.                                                                           131˜135°                                                          C. (4 mm Hg)                                                                 n.sub.D.sup.30                                                                1.4737                    5                                                                                   ##STR15##      pyrrolidine 0.03                                                                         30  1    30  3 87.2 bp.                                                                           102˜105°                                                          C. (2 mm Hg)                                                                 n.sub.D.sup.27                                                                1.4736                    6                                                                                   ##STR16##      3- melthylpyrrolidine 0.03                                                               30  1    30  4 88.3 bp.                                                                           93˜96°                                                           C. (2 mm Hg)                                                                  n.sub.D.sup.25                                                                1.4716                    7                                                                                   ##STR17##      pyrrolidine 0.05                                                                         30  1    30  3 90.4 bp.                                                                           90˜93°                                                           C. (2 mm Hg)                                                                  n.sub.D.sup.24                                                                1.4670                    8                                                                                   ##STR18##      pyrrolidine 0.01                                                                         30  3    30  4 93.8 bp.                                                                           129˜131°                                                          C. (0.01 mm Hg)                                                              n.sub.D.sup.31.5                                                              1.5181                    9                                                                                   ##STR19##      perhydroisoindole 0.03                                                                   5  1     5  1  91.5 bp.                                                                           101.5˜102.5.deg                                                         ree. C. (0.7 mm Hg)                                                           n.sub.D.sup.16                                                                1.5316                   10                                                                                   ##STR20##      3,4- dimethylpyrrolidine 0.05                                                            5  1    -5˜-15  5                                                                      93.5 bp.                                                                           101˜102°                                                          C. (0.03 mm Hg)                                                              n.sub.D.sup.17                                                                1.5517                   11                                                                                   ##STR21##      3- ethylpyrrolidine 0.03                                                                -5  1    -5  1  95.1 bp. 122° C.                                                            (0.7 mm                                                                       Hg) n.sub.D.sup.18                                                            1.5429                   12                                                                                   ##STR22##      perhydroisoindole 0.01                                                                  -5  1    -5  2  92.8 mp.                                                                           57˜62°                                                           C.                       13                                                                                   ##STR23##      pyrrolidine 0.03                                                                        -5  1    -6  15 95.9 mp.                                                                           81˜82°                                                           C.                       __________________________________________________________________________

EXAMPLE 14

Into a reaction vessel of 1 l in inside volume were placed 130.2 g (1mole) of 4-hydroxy-5-methyl-2-hexanone. 400 ml of toluene and 300 g of20% by weight aqueous H₂ SO₄ solution to heat to reflux for 3 hours.After the reaction was completed, the solution was cooled down to roomtemperature, and the aqueous layer was separated to remove. 150 ml ofwater was added to the organic layer, the pH was adjusted to 4.5 with28% aqueous NaOH solution, and the toluene and aqueous layers wereseparated. The toluene layer was concentrated. The obtained oily productwas distilled under reduced pressure to give 110.5 g of light yellowoily product with boiling point of 64° to 67° C. (30 mmHg) and n¹⁹ _(D)1.4428 (crude yield: 98.5%).

An analysis of the obtained product be gas chromatography revealed theintended product 5-methyl-3-hexene-2-one of 94.4% in purity. (Yield:93.0%, to 4-hydroxy-5-methyl-2-hexanone). An amount of remainingnon-reacted 4-hydroxy-5-methyl-2-hexanone was less than 0.1% and anamount of byproduct 5-methyl-4-hexene-2-one was 4.0%.

EXAMPLE 15 to 26

Example 14 was repeated except using different hydroxyketone under theconditions shown in Table 2. The results are shown in Table 2, includingthat of example 14.

                                      TABLE 2                                     __________________________________________________________________________     CompoundNo                                                                          ##STR24##        (ml/mole)Solvent                                                                    (g/mole)solutionacidAqueous                                                         (hr)timefluxRe-                                                                  material(%) toYield                                                                valuepropertyPhysical                                                                   (%)materialreactedho                                                         n-    (%)product.beta                                                              .γ            __________________________________________________________________________    14                                                                                   ##STR25##       toluene 400 ml                                                                      20% H.sub.2 SO.sub.4 300 g                                                          3  93.0 bp. 64˜67° C. (30                                                mm Hg) n.sub.D.sup.19                                                                   less                                                                               4.0n 0.1            15                                                                                   ##STR26##        toluene 400 ml                                                                     5% HCl 300 g                                                                        4  95.3 bp. 85˜88° C. (2                                                 mm Hg) n.sub.D.sup.23                                                                   0.8524                                                                             less than 0.1       16                                                                                   ##STR27##       toluene 400400 ml                                                                   5% HCl 300 g                                                                        4  96.0 bp. 80˜82° C. (1                                                 mm Hg) n.sub.D.sup.20                                                                   0.9858                                                                             1.4                 17                                                                                   ##STR28##       toluene 400 ml                                                                      20% H.sub.2 SO.sub.4 300 g                                                          3  92.5 bp. 91˜95° C.                                                    (0.1 mm Hg) mp.                                                               45˜46° C.                                                                  0.3  2.4                 18                                                                                   ##STR29##       toluene 400 ml                                                                      20% H.sub.2 SO.sub.4 300 g                                                          2  96.5 bp. 102˜103° C.                                                  (2 mm Hg) n.sub.D.sup.26                                                      1.4783    0.1  1.3                 19                                                                                   ##STR30##       chloroform 400 ml                                                                   5% HCl 400 g                                                                        4  94.2 bp. 92˜93° C.  (5                                                mm Hg) n.sub.D.sup.25                                                                   0.3709                                                                             1.8                 20                                                                                   ##STR31##       toluene 400 ml                                                                      20% H.sub.2 SO.sub.4 300 g                                                          2  93.8 bp. 78˜81° C. (3                                                 mm Hg) n.sub.D.sup.25                                                                   0.4820                                                                             1.5                 21                                                                                   ##STR32##       toluene 400 ml                                                                      20% H.sub.2 SO.sub.4 300 g                                                          3  95.0 bp. 107˜108° C.                                                  (0.1 mm Hg) n.sub.D.sup.32                                                    1.5320    1.5  1.3                 22                                                                                   ##STR33##       toluene 400 ml                                                                      20% H.sub.2 SO.sub.4 300 g                                                          2.5                                                                              93.2 bp. 81˜95° C.                                                    (0.6 mm Hg) mp.                                                               41˜42° C.                                                                  less                                                                               --an 0.1            23                                                                                   ##STR34##       toluene 400 ml                                                                      20% H.sub.2 SO.sub.4 300 g                                                          2  89.5 bp. 96˜103° C.                                                   (0.7 mm Hg)                                                                             4.9  --                  24                                                                                   ##STR35##       chloroform 400 ml                                                                   40% H.sub.2 SO.sub.4 300 g                                                          4  90.0 bp. 105˜108° C.                                                  (0.7 mm Hg) mp.                                                                         2.3about.59                                                                        --                  25                                                                                   ##STR36##       toluene 400 ml                                                                      20% H.sub.2 SO.sub.4 300 g                                                          3.5                                                                              94.3 mp. 106˜110°                                                               less                                                                               --an 0.1            26                                                                                   ##STR37##       toluene 400 ml                                                                      10% HCl 400 g                                                                       3  91.7 mp. 103.5˜106°                                                             less                                                                               --an 0.1            __________________________________________________________________________

EXAMPLE 27

Into a reaction vessel of 1 l in inside volume were placed 290.5 g (5moles) of acetone, 300 ml of water and 2.1 g (0.03 moles) ofpyrrolidine, to which 72.1 g (1 mole) of isobutylaldehyde was droppedover an hour which being kept at 30° C. for 1.5 hours.

After the reaction was completed, the solution was made pH 4.5 withC-sulfuric acid, and heated to distill up to distillation temperature100° C. 323.3 g of aqueous acetone solution was obtained as distillate.An analysis of the aqueous acetone solution by gas chromatography showed220.8 g of acetone (recovery: 76.0% Recovery was 95.0% if a mole ofacetone was regarded to be used for the reaction) and 102.5 g of water.

After it, to the residue, 400 ml of chloroform and 170.1 g ofC-hydrochloric acid were added and the mixture was refuxed for 2 hours.After the reaction, the reaction mixture was cooled to room temperatureand the aqueous solution layers were removed and to the chloroformlayers, 150 ml of water was added. After the mixture was made pH 4.5with 28% NaOH, the chloroform layers were separated and concentrated.The obtained oily product was distilled under reduced pressure to give92.3 g of light yellow oily product with boiling point of 61° to 64° C.at 28 mmHg and n_(D) ¹⁶.5 1.4439 (crude yield: 82.3%)

The product was analyzed by gas chromatography to find that the intendedproduct was 95.1% in purity.

EXAMPLES 28 TO 39

Example 27 was repeated except that the reaction was carried out using adifferent aldehyde under conditions shown in Table 3. The results areshown in Table 3, including that of Example 27.

                                      TABLE 3                                     __________________________________________________________________________     ##STR38##          aldehyde)amine/(mole ratiocatalystAmine                                               time (hr)(°C.)temperaturebeing                                        droppedWhile aldehyde                                                                  time (hr)(°C.)temperatureComple                                       tion    (ml/mole)dehydorationsolvent                                                 forAdding                                                                             (g/mole)dehydorationsolu                                                     tion forAquious                                                                       (hr)timeReflux                                                                    yield            __________________________________________________________________________    27                                                                               ##STR39##       pyrrolidine 0.03                                                                       30  1   30  1.5                                                                             chloroform 400                                                                       35% HCl 170                                                                          2   78.4              28                                                                               ##STR40##       perhydro- isoindole 0.05                                                               30   1  30  7 toluene 400                                                                          95% H.sub.2 SO.sub.4 59                                                       g      3   80.2              29                                                                               ##STR41##       3,3- dimethyl- pyrrolidine 0.03                                                        30  1   30  3 toluene 400                                                                          95% H.sub.2 SO.sub.4 59                                                       g      3   91.0              30                                                                               ##STR42##       pyrrolidine 0.03                                                                       30  1   30  3 toluene 400 ml                                                                       95% H.sub.2 SO.sub.4 60                                                       g      3   83.6              31                                                                               ##STR43##       pyrrolidine 0.05                                                                       30  1   30  2 toluene 400 ml                                                                       95% H.sub.2 SO.sub.4 60                                                       g      3   88.2              32                                                                               ##STR44##       3- ethylpyrrolidine 0.05                                                               30  1   30  3 chloroform 400                                                                       35% HCl 70                                                                           5   87.3              33                                                                               ##STR45##       pyrrolidine 0.05                                                                       30  1   30  3 toluene 400 ml                                                                       95% H.sub.2 SO.sub.4 60                                                       g      2   89.7              34                                                                               ##STR46##       pyrrolidine 0.03                                                                       30  1   30  5 toluene 400 ml                                                                       95% H.sub.2 SO.sub.4 59                                                       g      3   90.0              35                                                                               ##STR47##       3-methyl- pyrrolidine 0.03                                                             5  1    5  1  toluene 400 ml                                                                       95% H.sub.2 SO.sub.4 60                                                       g      2   89.8              36                                                                               ##STR48##       3,4-dimethyl- pyrrolidine 0.05                                                         5  1   -5˜-15  5                                                                      chloroform 400                                                                       20% H.sub.2 SO.sub.4 84                                                       g      2   83.7              37                                                                               ##STR49##       pyrrolidine 0.03                                                                      -5  1    -5  1 toluene 400 ml                                                                       95% H.sub.2 SO.sub.4 63                                                       g      4   85.6              38                                                                               ##STR50##       perhydro- isoindole 0.01                                                              -5  1   -5  2  toluene 400 ml                                                                       95% H.sub.2 SO.sub.4 59                                                       g      3   98.3              39                                                                               ##STR51##       pyrrolidine 0.03                                                                      -5  1   -6  1.5                                                                              toluene 400 ml                                                                       35% HCl 114                                                                          3   89.8              __________________________________________________________________________

INDUSTRIAL APPLICABILITY

This invention provides economically advantageous methods for thepreparation of the intended β-hydroxyketones (Compound I) andα,β-unsaturated ketones (Compound II) from an aldehyde with noα-hydrogen or with one α-hydrogen with high yield under gentle reactionconditions, being extremely significant in industry.

We claim:
 1. Method for preparing α,β-unsaturated ketone whichcomprises:(1) dehydrating a β-hydroxyketone of the formula (I) ##STR52##wherein R is (i) an aliphatic group having a side chain at the 1position, (ii) an alicyclic group optionally substituted, (iii) aheterocyclic group optionally substituted; or (iv) a phenyl groupoptionally substituted; (2) in the presence of an acid catalyst in asolvent mixture comprising water and a water-insoluble organic solventcompound (3) under conditions sufficient to thereby produce aα,β-unsaturated ketone of the formula (II) ##STR53## wherein R is asdefined above.
 2. Method for preparing α,β-unsaturated ketone whichcomprises:(1) reacting an aldehyde of the formula (III)

    RCHO                                                       (III)

wherein R is (i) an aliphatic group having a side chain at the 1position, (ii) an alicyclic group optionally substituted, (iii) aheterocyclic group optionally substituted, or (iv) a phenyl groupoptionally substituted; (2) with acetone, (3) utilizing a catalystcomprising perhydroisoindole or pyrrolidine or mixtures thereof, (4) inthe presence of water, (5) under condensation conditions sufficient tothereby produce a β-hydroxyketone of the formula (I) ##STR54## wherein Ris as defined above, and to remove unreacted acetone therefrom; (6)dehydrating the β-hydroxyketone (7) utilizing an acid catalyst in asolvent mixture comprising water and a water-insoluble organic solventcompound, (8) under conditions sufficient to thereby produceα,β-unsaturated ketone of the formula (II) ##STR55## wherein R is asdefined above.
 3. Method of producing α,β-unsaturated ketone whichcomprises(a) admixing acetone and a catalyst comprisingperhydroisoindole or pyrrolidine of the formula ##STR56## wherein R₁,R₂, R₃, and R₄ are hydrogen or lower aliphatic groups in an aqueoussolvent; (b) slowly introducing into the acetone-catalyst admixture analdehyde of the formula

    RCHO

wherein R is an aliphatic group having a side chain at the 1 position,an alicyclic group optionally substituted, a heterocyclic groupoptionally substituted, or a phenyl group optionally substituted, undercondensation conditions sufficient to react the acetone and aldehydethereby producing an aqueous solution of corresponding β-hydroxyketonereaction product; (c) removing unreacted acetone from the solution ofreaction product; (d) introducing an acid catalyst and a water insolubleorganic solvent into the aqueous reaction product under reactionconditions to convert β-hydroxyketone into the correspondingα,β-unsaturated ketone of the formula ##STR57## wherein R is as definedabove; and, (e) recovering α,β-unsaturated ketone in high purity.